Noninflammatory expression of E-selectin is regulated by cell growth

E-selectin, an endothelial-specific adhesion molecule best known for its ro le in leukocyte adhesion, is not detected in quiescent endothelial cells, b ut is induced by inflammatory stimuli. However, E-selectin is also expresse d in proliferating endothelial cells under noninflammatory conditions in vi vo and in vitro, suggesting that E-selectin is also regulated by growth sig nals. To investigate E-selectin expression in lipopolysaccharide-stimulated versus nonstimulated proliferating cells, we analyzed the distribution of E-selectin-positive human microvascular endothelial cells in G(0)/G(1), S, and G(2)/M phases of the cell cycle under both conditions. Lipopolysacchari de treatment resulted in uniformly increased E-selectin expression in cells in G(0)/G(1), S, and G(2)/M. In contrast, levels of E-selectin in nonstimu lated proliferating cells showed a linear correlation with the percentage o f cells in G(2)/M. E-selectin in proliferating endothelial cells was not re duced by addition of soluble tumor necrosis factor-alpha-receptor or solubl e interleukin-1-receptor indicating that its expression was not due to endo genous production of either cytokine. In addition, E-selectin was increased in cells stimulated with basic fibroblast growth factor, a well-known mito gen for endothelial cells. E-selectin in proliferating endothelial cells is functional, as shown by E-selectin-dependent adhesion of the promyelocytic leukemia cell line HL-60 to subconfluent human microvascular endothelial c ells. In summary, these studies indicate that E-selectin can be regulated b y a noninflammatory pathway that is related to the proliferative state of t he endothelium. (C) 1999 by The American Society of Hematology.